The signals and events required for maintaining serum antibodies to foreign and self- antigens remain poorly defined. The main goals of this application are to evaluate the role of recently formed antibody secreting plasma cells in the bone marrow (BM) in these processes, and to define the cytokines that recently formed and long-lived plasma cells employ to avoid cell death. To achieve these objectives we will: 1) Define the role of newly formed BM PCs in long-lived antibody-mediated immunity; 2) Define the role of newly formed and long-lived BM PCs in antibody-mediated autoimmunity; and 3) Define the roles of IL-5 and BAFF family cytokines in the maintenance of TI antigen-induced PCs. These studies will enhance knowledge of the processes underlying formation and maintenance of long-lived antibody responses to both non-self and self-antigens, and consequently inform strategies to optimize vaccination strategies and combat antibody mediated autoimmune disease. PUBLIC HEALTH RELEVANCE: The factors underlying the generation of long-lived antibody secreting plasma cells are not understood. These studies will define the role of persisting antigen in long-lived antibody-mediated immunity, while also challenging the current dogma that T cell independent antigens fail to induce the formation of long-lived plasma cells. These studies have direct implications for therapeutic strategies to combat antibody-mediated autoimmune diseases or conversely to induce long-lived immunity.